In field of contrast agents containing gadolinium, gadobutrol is commercially available in the world under brand name of Gadovist or Gadavist.
Gadobutrol represented by Formula 1 below is nonionic complex of microcyclic ligand 10-(2,3-dihydroxy-1-(hydroxymethyl)propyl)-1,4,7,10-tetraazacyclodecane-1,4,7-triacetic acid(butrol) and gadolinium(III), and specifically, it induces shortening of proton relaxation time of tissue fluid in a clinically recommended dose.

Three routes (schemes 1 to 3) for synthesizing gadobutrol are specifically disclosed in Inorg. Chem. 1997, 36, 6086-6093. The above reference discloses that the route of Scheme 3 is inadequate for a large scale production because of its low yield. Therefore, it is widely known to those skilled in the art that the route of Scheme 3 is only considerable for laboratory scale and it should be avoided for a large scale production. Meanwhile, the Scheme 1 requires large amount of resins for purification and it is disadvantageous because special facilities such as towers and the like should be provided for the purification. Therefore, the method of Scheme 1 is not applicable to large scale production due to increase of unit cost. In addition, the Scheme 2 has problems of low yield and poor purity.
International standards such as ICH Guidelines and the like recommend impurities content to be 0.1% or less, thus it is preferred to prepare ultra high-purity gadobutrol having purity of 99.9% or more for its sales as pharmaceuticals. However, the methods disclosed in the cited reference are complicated and high-purity gadobutrol cannot be prepared therefrom.
Therefore, a novel preparation method, therethrough high-purity gadobutrol can be prepared in high yield with simple preparation process unlike the conventional complicated process, has been required.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the present disclosure and it may therefore contain information that does not form the prior art that is already known to a person of ordinary skill in the art.